Evidence map›Paper›PMID 26337038›Full record

ArticleThe American journal of psychiatry2016

Dysregulated ErbB4 Splicing in Schizophrenia: Selective Effects on Parvalbumin Expression.

Daniel W Chung, David W Volk, Dominique Arion, Yun Zhang, Allan R Sampson, David A Lewis

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.

  1. Pre-frontal parvalbumin interneurons in schizophrenia: a meta-analysis of post-mortem studies.Journal of neural transmission (Vienna, Austria : 1996) · 2019
    Pooled it
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  13. Parvalbumin interneuron deficits in schizophrenia.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2024
    Review
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  18. Pharmacogenetic activation of parvalbumin interneurons in the prefrontal cortex rescues cognitive deficits induced by adolescent MK801 administration.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Article
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3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Daniel W ChungFrom the Translational Neuroscience Program, Department of Psychiatry, and the Medical Scientist Training Program, University of Pittsburgh School of Medicine; and the Department of Statistics, University of Pittsburgh.
David W VolkFrom the Translational Neuroscience Program, Department of Psychiatry, and the Medical Scientist Training Program, University of Pittsburgh School of Medicine; and the Department of Statistics, University of Pittsburgh.
Dominique ArionFrom the Translational Neuroscience Program, Department of Psychiatry, and the Medical Scientist Training Program, University of Pittsburgh School of Medicine; and the Department of Statistics, University of Pittsburgh.
Yun ZhangFrom the Translational Neuroscience Program, Department of Psychiatry, and the Medical Scientist Training Program, University of Pittsburgh School of Medicine; and the Department of Statistics, University of Pittsburgh.
Allan R SampsonFrom the Translational Neuroscience Program, Department of Psychiatry, and the Medical Scientist Training Program, University of Pittsburgh School of Medicine; and the Department of Statistics, University of Pittsburgh.
David A LewisFrom the Translational Neuroscience Program, Department of Psychiatry, and the Medical Scientist Training Program, University of Pittsburgh School of Medicine; and the Department of Statistics, University of Pittsburgh.
University of Pittsburgh · US

Funding

Statistics and Data Management CoreP50MH103204 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI OLSON, CARL ROGER · 2014 to 2018
$10.8M
SCHIZOPHRENIA AND CORTICAL DOPAMINE/GABA INTERACTIONSR01MH043784 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 1988 to 2023
$7.2M
GABA Neurons and Cortical Circuitry in SchizophreniaR37MH043784 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 2001 to 2010
$6.8M
Disrupted Ontogeny of Cortical GABA Neurons in SchizophreniaR01MH100066 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VOLK, DAVID W · 2014 to 2018
$2.2M
NIMH NIH HHS MH-043784NIMH NIH HHS MH-103204NIMH NIH HHS P50 MH103204NIMH NIH HHS R01 MH043784NIMH NIH HHS R01 MH100066NIMH NIH HHS R37 MH043784
6 · The paper itself

Abstract

objectiveAlternative splicing of ErbB4 transcripts is dysregulated in the dorsolateral prefrontal cortex in schizophrenia. ErbB4 regulates the activity of parvalbumin interneurons, and therefore dysregulated ErbB4 splicing could contribute to lower parvalbumin interneuron activity and consequently lower parvalbumin levels in schizophrenia. However, ErbB4 is also present in calretinin interneurons, which are not affected in schizophrenia. Therefore, the authors hypothesized that dysregulated ErbB4 splicing occurs selectively in parvalbumin interneurons and is associated with lower parvalbumin levels in schizophrenia.

methodTissue samples enriched in calretinin and parvalbumin interneurons were laser microdissected from dorsolateral prefrontal cortex layers 2 and 4, respectively, from matched pairs of schizophrenia and comparison subjects. Transcript levels for pan-ErbB4, four ErbB4 splicing variants (JM-a, JM-b, CYT-1, CYT-2), parvalbumin, and calretinin were quantified by quantitative polymerase chain reaction (qPCR) in each layer. Transcript levels for myocardial infarction associated transcript (MIAT), which regulates ErbB4 splicing, were quantified in gray matter by qPCR and in parvalbumin interneurons by microarray.

resultsCalretinin and parvalbumin mRNAs were preferentially expressed in layers 2 and 4, respectively. In schizophrenia subjects, lower parvalbumin levels, higher CYT-1 and JM-a levels, and lower CYT-2 and JM-b levels were detected selectively in layer 4. In layer 4, the JM-a/JM-b ratio was inversely correlated with parvalbumin levels in schizophrenia subjects. MIAT levels were preferentially higher in parvalbumin interneurons in schizophrenia subjects.

conclusionsThese findings suggest that elevated MIAT expression alters ErbB4 splicing selectively in parvalbumin interneurons in schizophrenia. Dysregulated ErbB4 splicing in schizophrenia may contribute to lower activity of parvalbumin interneurons and an activity-dependent down-regulation of parvalbumin expression.

Indexed as

SchizophreniaAdultAlternative SplicingDown-RegulationFemaleHumansInterneuronsMaleParvalbuminsPrefrontal CortexReceptor, ErbB-4ERBB4 protein, humanParvalbuminsReceptor, ErbB-4

Identifiers

PMID26337038
PMCPMC5242561
OpenAlexW2102125031

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.